This project proposes to study the metabolic pathways and biochemical mechanisms pertinent to the survival of mammalian spermatozoa, which, after ejaculation, are constantly exposed to nonideal and varied environments. Two conditions are recognized to be particularly threatening to sperm survival and contribute to its aging: 1) the presence of oxidizing agents and metabolic inhibitors in the ambient fluids and 2) exhaustion of exogenous metabolizable substrates, at which time the sperm must depend upon the utilization of endogenous stores of substrates for energy. Using ejaculated spermatozoa from the ram, dog and man, the roles of intracellular glutathione, glutathione reductase and glutathione peroxidase in protecting sperm cells from injurious agents such as hydrogen peroxide and heavy metals ions will be explored. The control mechanisms of the endogenous respiration of ejaculated sperm from these sources will be studied. Specifically, the roles of cyclic nucleotides, hormones and carnitine, and of zinc which is present in unusually large quantities in sperm, in controlling the rate and the extent of endogenous respiration and in the activation of endogenous lipid stores to yield utilizable fatty acids will be explored. These features of sperm metabolism are fundamental to sperm survival and fertility and the rational design of spermicidal agents for contraception.